PT  - JOURNAL ARTICLE
AU  - Miura, Takumi
AU  - Sugawara, Tohru
AU  - Fukuda, Atsushi
AU  - Tamoto, Ryo
AU  - Kawasaki, Tomoyuki
AU  - Umezawa, Akihiro
AU  - Akutsu, Hidenori
TI  - Generation of primitive neural stem cells from human fibroblasts using a defined set of factors
AID  - 10.1242/bio.013151
DP  - 2015 Nov 15
TA  - Biology Open
PG  - 1595--1607
VI  - 4
IP  - 11
4099  - http://bio.biologists.org/content/4/11/1595.short
4100  - http://bio.biologists.org/content/4/11/1595.full
SO  - Biology Open2015 Nov 15; 4
AB  - In mice, leukemia inhibitory factor (LIF)-dependent primitive neural stem cells (NSCs) have a higher neurogenic potential than bFGF-dependent definitive NSCs. Therefore, expandable primitive NSCs are required for research and for the development of therapeutic strategies for neurological diseases. There is a dearth of suitable techniques for the generation of human long-term expandable primitive NSCs. Here, we have described a method for the conversion of human fibroblasts to LIF-dependent primitive NSCs using a strategy based on techniques for the generation of induced pluripotent stem cells (iPSCs). These LIF-dependent induced NSCs (LD-iNSCs) can be expanded for >100 passages. Long-term cultured LD-iNSCs demonstrated multipotent neural differentiation potential and could generate motor neurons and dopaminergic neurons, as well as astrocytes and oligodendrocytes, indicating a high level of plasticity. Furthermore, LD-iNSCs easily reverted to human iPSCs, indicating that LD-iNSCs are in an intermediate iPSC state. This method may facilitate the generation of patient-specific human neurons for studies and treatment of neurodegenerative diseases.